The possibility of someday recording all the neurons firing in a
living creature’s central nervous system has inspired generations of
neuroscientists. Now a group of researchers at the Howard Hughes Medical
Institute has finally achieved the feat.
The scientists studied live zebrafish larvae that had been genetically encoded with a calcium indicator called
GCaMP5G. They suspended the larva in a gel and then beamed it with
lasers. Just before a neuron fires, its action potential is expressed
via a spike in calcium ions, so when one of the genetically modified
larva’s neurons reached its action potential, it glowed. This showed the
researchers the firing of the neurons without them having to attach a
bunch of electrodes to the fish.Over the course of an hour the researchers
used laser beams to scan the larva every 1.3 seconds, exciting the
retina of the zebrafish with each scan. This microscopy method
allowed the researchers to record up to 80 percent of the fish’s
100,000 neurons at single-cell resolution. This is the first time
scientists have recorded such a high percentage of an organism’s brain
activity at such a high resolution.

By seeing how the central nervous system works in its entirety in
real-time, the scientists could see complex neuronal connections. For
example, the researchers found that the activation of certain neurons in
the spinal cord overlapped with the activation of neurons known to be
associated with swimming, suggesting that the hindbrain-spinal network
is most likely involved in locomotion.

This new method of full central nervous system visualization allowed
the scientists to see the bigger picture of brain function, which
they published today in Nature Methods. Instead
of seeing a snapshot of brain activity in one lobe and trying to
correlate it with a particular function, this scanning method shows how
the coordinated firing of neurons in different parts of the brain and
spinal cord can cause a particular function.
Although the zebrafish larva’s brain is relatively small and simple,
the study demonstrates a new method that could be adapted to analyze
more complex central nervous systems in the future.